Several materials and approaches for tissue adhesives and sealants have emerged;however, substantial research attention is still required to fully realize the potential of materials that can be applied to a wound site in liquid form and solidify in situ, alleviating the need for sutures or bandages. Although radical-mediated polymerizations are an attractive means for fabricating materials for use in biological applications, owing to their ability to rapidly cure without solvent at room temperature, the majority of radical-mediated polymerizations are susceptible to oxygen inhibition. In the proposed work, oxygen initiates rather than inhibits the polymerization, therefore eliciting the counter effect. We propose novel, oxygen-mediated thiol-ene polymerization systems to address the shortcomings of current approaches to in situ polymerization for medical procedures. This approach for the initiation of thiol-ene polymerization is analogous to cyanoacrylate polymerization, where liquid monomer remains stable while in its packaging but, upon application to a wound site, cures rapidly. However, unlike cyanoacrylates, the chemical and mechanical properties of thiol-ene materials are readily varied. Initially, approaches for oxygen-mediated radical generation will be developed to initiate thiol-ene polymerization. Subsequently, thiol-ene resins, utilizing these oxygen-mediated initiation schemes for biomedical adhesives and sealants, will be formulated and benchmarked against commercial materials. Finally, modeling of the polymerization will be performed to guide and optimize formulation development with respect to application constraints such as thickness and temperature rise due to polymerization. PUBLIC HEALTH RELEVANCE: This project seeks to develop thiol-ene biomedical adhesives and sealants which polymerize upon exposure to oxygen. Utilizing thiol-ene systems, which demonstrate superior mechanical properties, biocompatibility, and ability to rapidly cure at ambient conditions, is expected to greatly improve upon both the utility and efficacy of existing materials.